Pharmacological evidence of a cholinergic contribution to elevated impulsivity and risky decision-making caused by adding win-paired cues to a rat gambling task.

PARASYMPATHOMIMETIC agents; IMPULSIVE personality; NICOTINIC agonists; LABORATORY rats; MUSCARINIC agonists; NICOTINIC receptors; TROPANES; OREXINS

Background: Pairing rewards with sensory stimulation, in the form of auditory and visual cues, increases risky decision-making in both rats and humans. Understanding the neurobiological basis of this effect could help explain why electronic gambling machines are so addictive, and inform treatment development for compulsive gambling and gaming. Numerous studies implicate the dopamine system in mediating the motivational influence of reward-paired cues; recent data suggest the cholinergic system also plays a critical role. Previous work also indicates that cholinergic drugs alter decision-making under uncertainty. Aims: We investigated whether the addition of reward-concurrent cues to the rat gambling task (crGT) altered the effects of peripherally administered cholinergic compounds. Methods: Muscarinic and nicotinic agonists and antagonists were administered to 16 male, Long–Evans rats trained on the crGT. Measures of optimal/risky decision-making and motor impulsivity were the main dependent variables of interest. Results: The muscarinic receptor antagonist scopolamine improved decision-making overall, decreasing selection of one of the risky options while increasing choice of the more advantageous options. The muscarinic agonist oxotremorine increased choice latency but did not significantly affect option preference. Neither the nicotinic antagonist mecamylamine nor the agonist nicotine affected choice patterns, but mecamylamine decreased premature responding, an index of motor impulsivity. Conclusions: These results contrast sharply from those obtained previously using the uncued rGT, and suggest that the deleterious effects of win-paired cues on decision-making and impulse control may result from elevated cholinergic tone. [ABSTRACT FROM AUTHOR]

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